Preserved adiposity in the Fisher 344 rat devoid of gut microbiota

Abstract

The gut microbiota is implicated in affecting host metabolism and energy regulation. Germ‐free (GF) C57BL/6 mice are extremely lean and resistant to diet‐induced obesity; an effect associated with increased intestinal fasting‐induced adipose factor (FIAF) and decreased hepatic lipogenesis. However, whether this altered metabolism observed in the absence of gut microbiota extends to other species commonly used to examine energy metabolism, is unknown. Thus, using the GF Fisher 344 rat, we examined adiposity and associated alterations in intestinal nutrient chemoreceptors and gut peptides, FIAF expression, and markers of hepatic and adipose lipogenesis. We found that, unlike GF mice, GF rats displayed similar body weights and adiposity relative to controls. Along with reductions in intestinal nutrient receptors and gut peptides, the GF state was associated with up‐regulation of intestinal and hepatic FIAF, decreased expression of hepatic FAS, ACC‐1, and SBREP and increased AMPK‐P and ACC‐1‐P. However, GF rats displayed reduced adipocyte FIAF and increased lipogenic enzymes, along with an increase in adipocyte size. These findings show that, despite similarly altered intestinal protein expression and reduced hepatic lipogenesis in the GF state, adiposity is normalized in the Fisher 344 GF rat, unlike the C57Bl/6J GF mouse, through enhancement of adipocyte lipogenesis leading to adipocyte hypertrophy.